CD99–PTPN12 axis suppresses actin cytoskeleton-mediated dimerization of epidermal growth factor receptor
- 주제(키워드) Actin cytoskeletal reorganization , Breast cancer , CD99 agonist , EGFR dimerization , Endocytosis , FAK dephosphorylation , PTPN12 , Rac1 , RhoA , Tripeptide
- 등재 SCIE, SCOPUS
- OA유형 Green Published, gold
- 발행기관 MDPI AG
- 발행년도 2020
- 총서유형 Journal
- URI http://www.dcollection.net/handler/ewha/000000174807
- 본문언어 영어
- Published As http://dx.doi.org/10.3390/cancers12102895
- PubMed https://pubmed.ncbi.nlm.nih.gov/33050232
초록/요약
The epidermal growth factor receptor (EGFR), a member of ErbB receptor tyrosine kinase (RTK) family, is activated through growth factor-induced reorganization of the actin cytoskeleton and subsequent dimerization. We herein explored the molecular mechanism underlying the suppression of ligand-induced EGFR dimerization by CD99 agonists and its relevance to tumor growth in vivo. Epidermal growth factor (EGF) activated the formation of c-Src/focal adhesion kinase (FAK)-mediated intracellular complex and subsequently induced RhoA-and Rac1-mediated actin remodeling, resulting in EGFR dimerization and endocytosis. In contrast, CD99 agonist facilitated FAK dephosphorylation through the HRAS/ERK/PTPN12 signaling pathway, leading to inhibition of actin cytoskeletal reorganization via inactivation of the RhoA and Rac1 signaling pathways. Moreover, CD99 agonist significantly suppressed tumor growth in a BALB/c mouse model injected with MDA-MB-231 human breast cancer cells. Taken together, these results indicate that CD99-derived agonist ligand inhibits epidermal growth factor (EGF)-induced EGFR dimerization through impairment of cytoskeletal reorganization by PTPN12-dependent c-Src/FAK inactivation, thereby suppressing breast cancer growth. © 2020 by the authors. Licensee MDPI, Basel, Switzerland.
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